Search results for "ddc:"
showing 10 items of 3080 documents
Resting-state posterior alpha rhythms are abnormal in subjective memory complaint seniors with preclinical Alzheimer's neuropathology and high educat…
2020
International audience; Cognitive reserve is present in Alzheimer's disease (AD) seniors with high education attainment making them clinically resilient to extended brain neuropathology and neurodegeneration. Here, we tested whether subjective memory complaint (SMC) seniors with AD neuropathology and high education attainment of the prospective INSIGHT-preAD cohort (Paris) may present abnormal eyesclosed resting state posterior electroencephalographic rhythms around individual alpha frequency peak, typically altered in AD patients. The SMC participants negative to amyloid PET AD markers (SMCneg) with high (over low-moderate) education level showed higher posterior alpha 2 power density (pos…
Initial serum thyroid peroxidase antibodies and long-term outcomes in SREAT.
2015
Objective To quantify clinical outcome in patients with steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) after the acute phase and explore potential associations of initial serum thyroid peroxidase antibody titers (TPO-Abs) with outcome. Materials and methods Retrospective chart review of patients diagnosed with SREAT between 01/2005 and 05/2014 in a tertiary care center and followed in an affiliated autoimmune outpatient clinic. Outcome was quantified using the extended Glasgow Outcome Scale (GOS-E). We calculated Pearson's correlation coefficients to quantify associations with clinical outcome at follow-up. Results Among 134 patients with encephalopathy of u…
The population genomics of archaeological transition in west Iberia: Investigation of ancient substructure using imputation and haplotype-based metho…
2017
We analyse new genomic data (0.05–2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200–3500 BC) to the Middle Bronze Age (1740–1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, t…
A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer
2018
Introduction IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. In vitro, IMAB362 mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity; thus, IMAB362 may serve as a potent, targeted immunotherapeutic agent. Methods This first-in-human phase I study enroled adult patients (N = 15) with advanced gastric or gastro-oesophageal junction cancer into five sequential single dose-escalation cohorts (33, 100, 300, 600, and 1000 mg/m2) following a 3 + 3 design. Safety/tolerability, including determination of maximum tolerated dose and recommended phase II dose, were the pr…
Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness
2017
Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10−8, METAL) of which 23 have not been reported previously. The 63 loci explain ∼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the de…
Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation
2016
Genome-wide study in Germans identifies four novel multiple sclerosis risk genes and confirms already known gene loci.
Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation
2018
Summary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and “toxic” gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function …
Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro…
2018
BACKGROUND: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. PATIENTS AND METHODS: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, …
A screen for constituents of motor control and decision making in Drosophila reveals visual distance-estimation neurons
2016
AbstractClimbing over chasms larger than step size is vital to fruit flies, since foraging and mating are achieved while walking. Flies avoid futile climbing attempts by processing parallax-motion vision to estimate gap width. To identify neuronal substrates of climbing control, we screened a large collection of fly lines with temporarily inactivated neuronal populations in a novel high-throughput assay described here. The observed climbing phenotypes were classified; lines in each group are reported. Selected lines were further analysed by high-resolution video cinematography. One striking class of flies attempts to climb chasms of unsurmountable width; expression analysis guided us to C2 …
Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever
2017
Arenaviruses such as Lassa virus (LASV) cause hemorrhagic fever. Terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. Here we used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (LCMV-WE), a close relative of LASV, to investigate the pathophysiology of arenavirus hemorrhagic fever (AHF). AHF manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic shock. A characteristic cytokine storm included numerous pro-inflammatory cytokines and nitric oxide (NO) metabolites. Edema formation and terminal shock were abrogated in mice lacking inducible nit…